Actuation indicator for a dispensing device

ABSTRACT

An actuation indicator that includes a drum sub-assembly, which includes a rotatable actuation indicator wheel, a rocking, ratchet pawl for rotating the indicator wheel in a set direction and a rocking mechanism for the pawl driven by a slipping clutch arrangement, is described. The slipping clutch arrangement includes a slipping clutch spring engaged at one end to a pinion of a rack and pinion assembly and at a second end to the ratchet pawl.

RELATED APPLICATION

The present application claims priority from UK patent application No.0214360.0 filed 21 Jun. 2002 and UK patent application No. 0311191.1filed 15 May 2003, the entire contents of which are hereby incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention relates to an actuation indicator for a dispensingdevice, e.g. a fluid dispensing device or pressurised fluid dispensingdevice, such as a pressurised metered dose inhaler (hereinafter referredto as a “pMDI”), and components of such an actuation indicator.

BACKGROUND OF THE INVENTION

“pMDIs” are well known in the art of inhalation devices. It is thereforenot necessary to describe the construction and operation of a PMDI otherthan in bare essentials.

A PMDI comprises an aerosol canister and a tubular actuator.

The aerosol canister comprises a pressurised can, typically made from ametal, such as aluminium. Inside the can there is contained thepressurised medicinal aerosol formulation. The can is sealingly cappedby a metering valve assembly at what will hereinafter be referred to asthe “outlet end” of the aerosol canister. The valve assembly includes ahollow dispensing member or valve stem which projects from the outletend of the aerosol canister. The dispensing member is mounted forsliding movement relative to the aerosol canister between an extendedposition, to which the dispensing member is biased by a biasingmechanism in the valve assembly, and a depressed position.

Movement of the dispensing member from the extended position to thedepressed position results in a metered dose of the aerosol formulationbeing dispensed from the canister through the dispensing member.

The tubular actuator comprises an internal passageway having an openend. The aerosol canister is slidable into the internal passagewaythrough the open end with the outlet end being inserted first into theinternal passageway.

The actuator has a stand or stem block which receives the dispensingmember of the aerosol canister when the aerosol canister is received inthe actuator in a “rest position”. The stand has a passageway with aninlet end for receiving the dispensing member and an outlet end whichfaces a mouthpiece of the actuator. The stand holds the dispensingmember stationary in the actuator whereby depression of the aerosolcanister from its rest position farther into the actuator to an“actuated position” causes the dispensing member to be displaced fromthe extended position to the depressed position relative to thecanister. A metered dose of the aerosol formulation will thereby bedispensed out of the mouthpiece of the actuator via the internalpassageway of the stand.

In use, a patient in need of a metered dose of the medicinal aerosolformulation places their lips on the mouthpiece of the actuator and thenconcurrently inhales and depresses the aerosol canister from the restposition to the actuated position. The inspiratory airflow produced bythe patient entrains the medicinal, component of the aerosol into thepatient's respiratory tract.

Instead of a mouthpiece, there could be provided a nozzle for nasal use.

Developments to these pMDIs have included the provision of actuationindicators therefor, for instance dose counters which are eitherincremented on each actuation of the pMDI to display a running total ofthe number of doses dispensed from the PMDI or decremented on eachactuation to display the number of doses left in the dispenser. See, forexample, W096/16686, US-A-4817822 and U.S. Pat. No. 5,482,030.

A recently developed dose counter is described in PCT Patent ApplicationNo. W098/56444, to Glaxo Group Limited, the entire contents of which areincorporated herein by way of reference. The dose counter is fixablysecured on the outlet end of the aerosol canister and includes a displaywhich denotes the number of metered doses of the medicament formulationleft in the aerosol canister. The display of the dose counter is visibleto the patient through a window provided in the actuator. The display ispresented by a plurality of indicator wheels rotatably mounted on acommon axle, each wheel having numerals from ‘0’ to ‘9’ displayed inseries around the circumference.

Before the dose counter is mounted on the aerosol canister, the displaywheels are arranged so that the display shows the claimed total numberof doses available in the aerosol canister, the so-called “label claim”.Upon each actuation, an indexing mechanism in the dose countercomprising a star wheel, a driver yoke and a rack operates to decrementthe number displayed by the display by rotation of one or more of theindicator wheels.

When the aerosol canister with attached dose counter is in a restposition in the actuator, the rack, which is formed in the actuator,protrudes into the dose counter. When the aerosol canister is moved fromthe rest position to the actuated position, this results in relativemovement between the dose counter and the rack. During this relativemovement, the rack engages the yoke of the indexing mechanism to causeit to operate to decrement the number displayed by the display byturning the star wheel. The index mechanism of the mechanical dosecounter known from W098/56444 includes a lost motion coupling tocompensate for overtravel of the dose counter relative to the rack asthe aerosol canister reciprocates between the rest position and theactuated position in the actuator.

A device and method for attaching a dose counter to an aerosol canisteris disclosed in PCT application publication WO01/28887, also to GlaxoGroup Limited, the entire contents of which are incorporated herein byway of reference. The dose counter is fixedly secured to the outlet endof the aerosol canister through a split-ring collar. More particularly,a skirt portion of the dose counter housing surrounds a neck on the canof the aerosol canister, and the split-ring collar is wedged in-betweenthe skirt and a re-entrant surface of the neck and then ultrasonicallywelded to the skirt. This effectively provides a permanent connectionbetween the dose counter and the aerosol canister to prevent the dosecounter from being tampered with.

All these prior art devices, however, require the components thereof tobe manufactured to tight tolerances so that they correctly function, orthey are difficult to assemble. Accordingly, they are relativelyexpensive to manufacture. Further, they are unsuitable for attachment tocanisters or actuators that are made with wide manufacturing tolerances,as may occur when attempting to reduce the manufacturing cost ofactuators or aerosol canisters.

It would be desirable to provide an actuator and/or dose counter that isinexpensive to manufacture due to the lack of the need for tightmanufacturing tolerances. It would also be desirable to provide anactuator and/or dose counter that is simple and therefore inexpensive toassemble. It would also be desirable to provide an actuator and/or dosecounter that can be used with more than one size of aerosol canister. Itwould also be desirable to provide components of such devices that allowfor wide manufacturing tolerances.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention there is providedan axle of a rotatable element of an actuation indicator (e.g. a dosecounter), wherein the axle is provided by a spring that is adapted inuse to bias the rotatable element towards another element of theactuation indicator with which the rotatable element is engaged. Theother element may be for causing rotation of the rotatable element, orcaused to be rotated by the rotatable element. This biasing allows thetwo elements to be made with wide tolerances while still being able tooperate correctly together.

Preferably the rotatable element is a pinion.

Preferably the other element with which the pinion engages is a rack,for instance extending through the dose counter.

Preferably the rotatable element is an indicator wheel for indicatingactuation of a device with which the indicator is associated, e.g. forindicating at least a part of a count of the number of doses of asubstance left in, or dispensed from, a dispensing device.

Preferably there are at least two rotatable elements on the axle, forinstance three rotatable elements as in the exemplary embodimenthereinafter to be described. The rotatable elements may respectively bea units wheel and a tens wheel, and hundreds wheel where there is athird rotatable element, for indicating a dose count.

Preferably the other element is a rotatable element mounted on a second,preferably parallel, axle. More preferably, the second axle is alsoprovided by the spring.

The present invention further provides an axle assembly comprising theaxle, the rotatable element(s) on the spring axle and the other element.

Preferably the spring also comprises a biasing section which connectsthe axles and biases the axles towards one another. The section may (i)be U-shaped, (ii) have substantially parallel sides and (iii) besubstantially perpendicular to the two axles.

The present invention further provides an actuation indicator comprisinga drums sub-assembly comprising a rotatable actuation indicator wheel, arocking, ratchet pawl for rotating the indicator wheel in a setdirection and a rocking mechanism for the pawl driven by a slippingclutch arrangement, wherein the slipping clutch arrangement comprises aslipping clutch spring engaged at one end to a pinion of a rack andpinion assembly and at a second end to the ratchet pawl.

Preferably the slipping clutch spring has a generally U-shapedconfiguration.

Preferably the open end of the spring engages a boss of the pinion andthe closed end of the spring defines a track for slidingly engaging aboss provided on the pawl.

Preferably the ratchet pawl engages a ratchet wheel that is fixed to theindicator wheel.

Preferably a resilient, non-return leg engages a tooth of the ratchetwheel to prevent rotation of the ratchet wheel in a direction other thanthe set direction, and the non-return leg rides up and over the teeth toallow rotation in the set direction.

Preferably there are at least two indicator wheels arranged tosequentially count down from a set figure to zero, there being at leasta tens wheel and a units wheel, wherein the indicator wheels lock fromfurther rotation in the set direction when they have counted down tozero, the slipping clutch spring then slipping upon further attempts torotate the mechanism.

The present invention also provides a casing adapted to be attached overa valve stem end of a canister to form a canister unit, the casingcomprising a sleeve part having a generally cylindrically shaped sectionhaving a generally cylindrical inner surface extending from a top of thesleeve part towards a base wall, and a collar affixable around a neck ofthe canister, and sized, when around the neck of the canister, to fitthrough the top of the sleeve part, into the sleeve part, whereat itwill contact at least a portion of the generally cylindrical innersurface, wherein the generally cylindrical inner surface has a shoulderfor supporting the collar to prevent the collar from being insertedfurther into the sleeve part, the shoulder being spaced from the top andthe base wall of the sleeve part.

In accordance with the invention in all its aspects, the canister unitmay be a pressurised canister unit, such as an aerosol canister unit,e.g. for use in a pressurised metered dose inhaler.

Preferably the top of the sleeve part comprises a chamfered surface toassist with the insertion of the collar into the sleeve part.

Preferably the shoulder is formed by an annular step in the generallycylindrical inner surface.

Preferably the shoulder is formed by a ledge attached to the generallycylindrical inner surface.

Preferably the collar is a split ring collar.

Preferably the collar, in an assembled canister unit, is welded to thesleeve part.

The present invention also provides a casing adapted to be attached overa valve stem end of a canister to form a canister unit, the casingcomprising a sleeve part for receiving a canister and a cap part forreceiving a counter assembly of a dose counter for the canister unit,wherein the cap part and counter assembly can be assembled togetherseparate from the sleeve part and canister, the sleeve part and cap partthen being joinable together to form the casing.

Preferably, the casing further comprises a counter assembly, the counterassembly comprising a drums sub-assembly.

Preferably the sleeve part is adapted to receive more than one form ortype of valve stem end, e.g. pressurised fluid canisters fitted withdifferent valves.

Preferably the sleeve part comprises a top through which, in use, avalve stem end of the canister will be inserted and a base wall spacedfrom the top having more than one support thereon, each support beingfor supporting a different form of valve stem end, whereby more than onedifferent valve stem end can be supported in the sleeve part.

Preferably the supports are annular ledges.

Preferably the ledges are concentric.

Preferably a first said support is of a first height above the base walland a second said support is of a lesser height above the base wall.

The present invention also provides components for the above casingcomprising a cap part and at least two sleeve parts, the two sleeveparts being for different valve stem ends, wherein the cap part isjoinable to any one of the sleeve parts to form a casing for a chosenvalve stem end.

The present invention also provides a sleeve part for receiving a valvestem end of a canister, the sleeve part being adapted to receive morethan one form of valve stem end.

Preferably the sleeve part comprises a top through which, in use, avalve stem end of the canister will be inserted and a base wall spacedfrom the top having more than one support thereon, each support adaptedfor supporting a different form of valve stem end, whereby more than onedifferent form of valve stem end is able to be supported in the sleevepart.

Preferably the supports are annular ledges.

Preferably the ledges are concentric.

Preferably a first support is of a first height above the base wall andthe second support is of a lesser height above the base wall.

The present invention further provides a drug product for dispensing adrug formulation comprising a propellant and a medicament comprising:

-   -   a housing;    -   a container containing the drug formulation having an outlet        member and adapted to be actuable within the housing; and,    -   an actuation indicating assembly, fixedly attached to the        container, comprising:    -   a body cradle having a post;    -   a drive wheel adapted to engage the post and to frictionally        engage a slipping clutch;    -   a ratchet pawl adapted to engage the slipping clutch;    -   a star wheel adapted to engage the ratchet pawl; and    -   one or more drums adapted to engage the star wheel;    -   wherein the fixedly attached container and actuation indicating        assembly are reversibly removable from the housing as a single        unit.

Preferably there are three drums adapted to display a count of 000 to999. Preferably, the product further comprises an arm affixed to ahundred's drum adapted to contact a stop, wherein the slipping clutch isadapted to frictionally slip when the count reaches 000.

Preferably the drug product comprises a hundred's drum having numerals0, 1 and 2, a ten's drum having numerals 0 through 9 and a one's drumhaving numerals 0 through 9.

Preferably the actuation indicating assembly includes one or more gripmembers adapted to fixedly engage a neck portion of the container.

Preferably the housing includes a mouthpiece.

Preferably the housing includes a passage adapted to pass doses from thecontainer to the mouthpiece.

Preferably the container includes a metering valve adapted to dispensemetered doses.

Preferably a window is provided, adapted to display numerals on one ormore drums engaging the star wheel.

Preferably the actuation indicating assembly is fixed to the containerby an adhesive, a welded shrink sleeve, a heat form, a crimp, anultrasonic weld, an o-ring elastomer, or a split-ring collar.

Preferably the actuation indicating assembly is permanently fixed to thecontainer.

Preferably the medicament is selected from the group consisting ofbeclomethasone, fluticasone, flunisolide, budesonide, rofleponide,mometasone, triamcinolone, noscapine, albuterol, salmeterol, ephedrine,adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol,terbutaline, tiotropium, ipratropium, phenylephrine,phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine,tulobuterol,(-)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl}methyl}benzenemethanol,esters, solvates and salts thereof, and combinations thereof.

Preferably the medicament is albuterol sulphate, salmeterol xinafoate,fluticasone propionate, beclomethasone dipropionate or the combinationof salmeterol xinafoate and fluticasone propionate. The medicament mayalso be salmeterol xinafoate and a salt, ester or solvate ofipratropium.

Preferably the housing is constructed from polypropylene.

Preferably one or more components of the actuation indicating assemblyis constructed from polypropylene. Preferably the drug product furthercomprises one or more knock gears adapted to engage the one or moredrums.

Preferably the drug product comprises first, second and third drums andfirst and second knock gears.

The present invention also provides a method of patient compliancecomprising the acts of:

-   -   providing a drug product as described above,    -   administering the drug formulation to a patient,    -   counting down a number of available doses remaining in the        container on the actuation indicating assembly, and,    -   indicating the number of available doses remaining in the        container to the patient.

Preferably the container is over-filled with up to 40 actuations.

Preferably the actuation indicating assembly locks out when the countreaches 000, and wherein the drug product remains actuable for up to 40subsequent actuations.

The present invention further provides a drug product for dispensing adrug formulation comprising a propellant and a medicament comprising:

-   -   a housing;    -   a container containing the drug formulation having an outlet        member and adapted to be actuable within the housing; and,    -   an actuation indicating assembly, fixedly attached to the        container, comprising:    -   a body cradle having a post;    -   a means for driving a slipping clutch means adapted to engage        the post and to frictionally engage the slipping clutch means        for grasping a ratcheting means;    -   a pawl means for ratcheting a star wheel adapted to engage the        slipping clutch means;    -   a star wheel adapted to engage the pawl ratcheting means; and    -   one or more drums adapted to engage the star wheel;    -   wherein the fixedly attached container and actuation indicating        assembly are reversibly removable from the housing as a single        unit.

Preferably the drug product comprises first, second and third drums.Preferably the drug product further comprises a means for stopping thefirst drum.

Preferably the drug product further comprises a first means for knocklocking the first and second drums and a second means for knock lockingthe second and third drums.

Preferably the drug product is further adapted to indicate a count of000 to 999 and further adapted to lock the drums when the countindicates 000.

The present invention further provides a dispensing device, e.g. fordispensing a fluid, on which is mounted an actuation indicator eitheraccording to the invention or having one or more of the differentaspects of the invention as a component thereof. The actuation indicatorwill be adapted to be operated upon each actuation of the dispensingdevice to indicate said actuation of the device. Preferably, theactuation indicator will be in the form of a dose counter which displaysa numerical count of the number of doses of the content of the deviceleft to be dispensed, or the number of doses dispensed. On actuation ofthe device, the numerical count is either incremented or decremented,depending on whether the count is of doses left or of doses dispensed.Preferably, the dispensing device has a dispensing or outlet end and theactuation indicator is mounted on this end. Preferably, the dispensingdevice is an aerosol canister having a can and a valve assembly at theoutlet end. The valve assembly may be a metering valve assembly, as forexample where for use in a pressurised metered dose inhaler.

These and other aspects of the present invention will now be describedby way of example with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic perspective view of a pressurised metered doseinhaler (PMDI) having a dose counter module mounted on the outlet end ofan aerosol canister unit containing a pressurised medicinal aerosolformulation.

FIG. 2 is an exploded perspective view of the dose counter module.

FIG. 3 is a further exploded perspective view of the dose countermodule, but with a drums sub-assembly and drive wheel sub-assembly ofthe dose counter in assembled form.

FIG. 4 is a first perspective view of a cap part of the dose countermodule with the drums sub-assembly and drive wheel sub-assembly mountedtherein.

FIG. 5 is a second perspective view of the cap part from an oppositedirection to that of FIG. 4, with a clutch spring fitted thereto.

FIG. 6 is a yet further perspective view of the cap part.

FIG. 7 is a perspective front view of the drums sub-assembly.

FIG. 8 is a schematic perspective view of the dose counter module insidean actuator of the pMDI, showing the drums and drive wheelsub-assemblies and a rack formed inside the actuator through which thedrive wheel sub-assembly is driven.

FIG. 9 is a schematic rear perspective view of the drive wheelsub-assembly showing a toggle link-type lost motion coupling throughwhich drive from the drive wheel sub-assembly is transmitted to thedrums sub-assembly.

FIGS. 10 to 13 are schematic views showing the sequence of steps bywhich the drive wheel sub-assembly drives the drums sub-assembly.

FIGS. 14A-F are a series of views illustrating how the knock gears ofthe drums sub-assembly transmit rotation from one drum to another todecrement the number displayed by the drums sub-assembly.

FIGS. 15A-B are schematic views illustrating the operation of the knockgears.

FIGS. 16A-F are a series of views illustrating how the drumssub-assembly reaches a “lockout” state in which the number displayed bythe counter is not able to be advanced, while allowing continuedactuation of the aerosol canister.

FIGS. 17A-B are schematic views illustrating the lockout operation.

FIG. 18 is a perspective view of a sleeve part in accordance with theinvention for a casing of a canister unit having a diameter ofapproximately 22 mm.

FIG. 19 is an end view of the sleeve part of FIG. 18 viewed in thedirection of arrow A.

FIG. 20 is an end view of the sleeve part of FIG. 18 viewed in thedirection of arrow B.

FIG. 21 is a section of the sleeve part through line B of FIG. 19.

FIGS. 22 and 23 are sections through a pMDI having a canister unitinserted in an actuator, the canister in

FIG. 22 having a valve of a first configuration and the canister in FIG.23 having a valve of a second, different configuration.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a pressurised metered dose inhaler, or PMDI, 1. The PMDI 1comprises a tubular actuator 3 of a generally L-shape. The actuator 3 isprovided with an open-ended through passage or internal passageway 5which extends from an upper opening or open end 7 to a lower opening(not shown) in a mouthpiece 9. The actuator further comprises a viewingwindow 11.

The pMDI 1 further comprises an aerosol canister unit 15, whichcomprises an aerosol canister 17, shown in ghost and having a standardconstruction as described in the ‘Background of the Invention’ sectionabove, and a dose counter module 19 mounted on the outlet end of thecanister 17. The aerosol canister 17 contains a pressurised medicinalaerosol formulation, for example a therapeutic agent suspended ordissolved in a liquified gas propellant, typically a hydrofluoroalkane(HFA) propellant, such as HFA-134 a or HFA-227.

As will be understood from the ‘Background of the Invention’ sectionabove, the aerosol canister unit 15 is adapted to be slid into thepassageway 5 of the actuator 3 through the upper opening 7 when theaerosol canister unit 15 is inverted, i.e. with the dose counter module19 at the leading end, so that it is inserted first into the actuator 3.

The aerosol canister unit 15 is slid along the passageway 5 to a restposition in which a dispensing member (not shown) of the aerosolcanister 17, which projects into the dose counter module 19, engages astand (not shown) in the passageway 5 so that the dispensing member isheld stationary in the actuator 3. Further depression of the aerosolcanister unit 15 into the passageway 5 causes the dispensing member tobe depressed into the aerosol canister 17 and a metered dose of themedicinal aerosol formulation will then be dispensed from the aerosolcanister 17. The dose will thereby be exhausted from the actuator 3through the mouthpiece 9.

For correct angular orientation of the aerosol canister unit 15 in theactuator 3, the passageway 5 defines a longitudinal inner track portion21 to receive a complementary protrusion 23 on the outer circumferentialsurface of the dose counter module 19. The protrusion coincides with adisplay window 25 of the dose counter module. The window 11 of theactuator 3 is located in the wall of the longitudinal track portion 21to ensure that the display window 25 on the protrusion 23 registers withthe window 11 of the actuator 3. A patient can thereby view the displayin the dose counter window 25 when the aerosol canister unit 15 ismounted in the actuator 3.

Referring to FIGS. 1 and 2, the dose counter module 19 has a hollowouter casing 30 made from a plastics material, for example polypropylene(PP). As shown in FIG. 2, the outer casing 30 is formed from a cap part31 and a sleeve part 33. The cap part 31 has a plurality of posts 35which project upwardly (in inverted orientation) from the periphery ofthe cap part 31. They are provided to extend through alignment holes(not shown) in the sleeve part 33. The posts 35 are subsequently joinedor adhered to an inner surface of the sleeve part 33, for example bywelding, such as ultrasonic welding. This ensures a permanent connectionof the cap part 31 to the sleeve part 33.

The cap and sleeve parts 31,33 both comprise elements of the protrusion23 of the dose counter module 19. The window 25 is retained in a track39 formed in those elements of the protrusion 23 when the cap and sleeveparts 31, 33 are mated together. The window may be made of a transparentplastics material, for instance polymethyl methacrylate (PMMA), such asPERSPEX (RTM).

As shown in FIGS. 2 to 6, the cap part 31 has a generally U-shape crosssection. When the dose counter module 19 is mounted to the outlet end ofthe aerosol canister 17, the dispensing member (not shown) of theaerosol canister 17 is received in the concave cut-out 41 of theU-shaped cap part 31. Moreover, when the aerosol canister unit 15 isslid into the actuator 3 to its rest position, the stand is received inthe cut-out 41 for engagement with the dispensing member. In otherwords, the cap part 31 of the dose counter module 19 is arranged aboutthe stand. See W098/56444, and in particular FIG. 1 thereof, for afuller disclosure of the dispensing member and the stand therefor.

Turning to FIG. 2, when the dose counter module 19 is assembled, it ismounted to the outlet end of the aerosol canister 17 through asplit-ring collar 43, for example made of PP, which is mounted to theneck on the can of the aerosol canister 17 and then wedged between theneck and an inner circumferential surface 45 of the sleeve part 33 ofthe outer casing 30 prior to welding it thereto by ultrasonic welding,as further detailed in WO-A-0128887, supra.

The outer casing 30 of the dose counter module 19 houses a mechanicaldose counting mechanism, details of which now follow.

As shown in FIG. 4, the cap part 31 of the outer casing 30 retains adrums sub-assembly 50 of the counting mechanism. Referring also to FIG.2, the drums sub-assembly 50 comprises an axle spring 51 having an upperaxle 53, a lower axle 55, which extends parallel to the upper axle 53,and a U-shaped connector section 57 oriented perpendicularly to theupper and lower axles 53,55. The axle spring 51 is made from a metal,such as a stainless spring steel. The connector section 57 operates tobias the upper and lower axles 53, 55 to a closed position, i.e. towardsone another.

The drums sub-assembly 50 further comprises a set of three indicatorwheels 59, 61, 63 which are adapted to be co-axially mounted on theupper axle 53 for rotation thereon. The indicator wheels 59, 61, 63 areformed from a plastics material, e.g. acetal, ideally by injectionmoulding. Each indicator wheel 59, 61, 63 is provided with a centralaperture 60, 62,6 4 to enable them to be slid onto the upper axle 53 ofthe axle spring 51.

Each indicator wheel 59, 61, 63 has numbers arranged circumferentiallyin order on the rims 65, 67, 69 of the wheels 59, 61, 63, applied forexample in the manner disclosed in International patent applicationpublication WO-A-0108733, also to Glaxo Group Limited.

The rotational position of each indicator wheel 59, 61, 63 on the upperaxle 53 determines which number on its rim 65, 67, 69 is displayedthrough the window 25 of the dose counter module 19. The indicatorwheels 59,6 1, 63 collectively display a three digit number in thewindow 25, which number identifies the number of metered doses of themedicinal aerosol formulation left in the aerosol canister 17. Thus, atthe outset, i.e. before use, the indicator wheels 59, 61, 63 arearranged on the upper axle 53 so that the three digit number displayedin the window 25 corresponds to the label claim of metered dosesavailable in the aerosol canister 17.

It is convenient to refer to the right-hand indicator wheel 59 (asviewed in e.g. FIG. 7) as the “units wheel”, the central indicator wheel61 as the “tens wheel” and the left-hand indicator wheel 63 as the“hundreds wheel” because the numbers displayed thereon correspond to theunits, tens and hundreds of the dose count displayed in the window 25.

It will be appreciated that the use of three indicator wheels 59, 61, 63enables the dose counter module 19 to be used with an aerosol canisterwhich is filled with over one hundred metered doses of a medicinalaerosol formulation. As will be understood, the number of indicatorwheels could be increased or decreased depending on the number ofmetered doses in the aerosol canister 17. For instance, if the “labelclaim” was less than a hundred metered doses, it may be convenient touse only two indicator wheels. Of course, three indicator wheels couldstill be used.

In this embodiment, the units and tens wheels 59, 61 each have thenumbers ‘0’ to ‘9’ inclusive equi-angularly arranged thereon in series,while the hundreds wheel 63 only has the numbers ‘0’ to ‘2’ inclusivearranged thereon in series, although with the same inter-number angularspacing (36°) as for the numbers on the units and tens wheels 59, 61. Ofcourse, the series of numbers on the hundreds wheel 63 can be increasedor decreased, depending on the “start count” desired.

As shown in FIGS. 2 and 5, the units wheel 59 has a ratchet wheel 71 onits right-hand side which is provided with teeth 74 on its circumference73. The ratchet wheel 71 is supported on the end of a shaft 72 (seeFIGS. 7 and 14B). Referring now to FIGS. 7, 14F and 15A, the left-handside of the units wheel 59 is provided with a boss 75 provided with justtwo teeth (a “bunny” tooth 77). As shown in FIG. 2, the tens wheel 61and the hundreds wheel 63 each have a boss 79, 81 on the right-hand sidewith a toothed circumference 83, 85. FIG. 7 shows that the toothedcircumferences 83, 85 have teeth 87,89 whose tips are flush with therims 67, 69 of the associated indicator wheel 61,63. As shown in FIGS. 7and 14F, the tens wheel 61 is further provided with a boss 91 on itsleft-hand side which is also provided with a bunny tooth 93 on its outercircumference 95.

As further shown in FIGS. 7 and 14F, as well as FIG. 4, the hundredswheel 63 has a boss 97 having an outer circumference 99 provided with aradially protruding segment 101 which lies flush with the rim 69 of thehundreds wheel 63.

Referring to FIG. 2, the drums sub-assembly 50 further comprises a setof two knock gears 103,105 having axial apertures 107,109 which enablethe knock gears 103, 105 to be co-axially mounted on the lower axle 55of the axle spring 51 for rotation thereon. As shown in FIG. 7, forexample, each knock gear 103,105 has a toothed wheel portion 111, 113, adisc portion 115,117 arranged parallel to the associated toothed wheeledportion 111, 113, but axially offset therefrom, and an axially-arrangedhollow shaft portion 119, 121 which connects the associated toothedwheel and disc portions 111, 113:115, 117. The knock gears are made of aplastics material, e.g. acetal, and are ideally made by injectionmoulding.

The disc portions 115, 117 of the knock gears 103, 105 function tolocate the knock gears and indicator wheels correctly in the cap part31. In particular, the disc portions 115, 117 inhibit axial play of theindicator wheels and knock gears on the axle spring 51 by overlappingthe outer surfaces of the units and hundreds wheels 59, 63, on the onehand, and being overlapped by surface features in the cap part 31 (notshown), on the other hand. So, neither the indicator wheels 59, 61, 63nor the knock gears 103, 105 can be outwardly axially displaced on thespring axle 51 once located in the outer casing 30.

As further shown in FIG. 7, the toothed wheeled portions 111, 113 of theknock gears 103, 105 are divided into two axial sections, a right-handside section 123, 125 and a left-hand side section 127, 129. The numberof teeth presented by the right-hand side sections 123, 125 (4 teeth) isless than the number of teeth presented by the left-hand side sections127, 129.

As will be understood from FIG. 7, when the indicator wheels 59, 61, 63and knock gears 103, 105 are mounted on the upper and lower axles 53,55, respectively, the rims 65, 67 of the units and tens wheels 59, 61are rotatably supported between adjacent teeth in the right-hand sidesections 123, 125 of the toothed wheeled portions 111, 113 of the knockgears 103, 105. Moreover, the teeth 87, 89 on the tens wheel 61 and thehundreds wheel 63 mesh with the teeth of the left-hand side sections127, 129 of the toothed wheel portions 111, 113 of the knock gears 103,105.

As will be further understood from FIG. 7, for example, the inherentbiasing force in the axle spring 51 ensures that the indicator wheels59, 61, 63 and knock gears 103, 105 are biased towards one another sothat the interengagable circumferential surfaces thereof interengage oneanother. In other words, the upper and lower axles 53, 55 need to beparted against the action of the biasing force to accommodate theindicator wheels 59, 61, 63 and knock gears 103, 105. Thus, in theassembled state of the drums sub-assembly 50, the upper and lower axles53, 55 are spaced apart by a distance which is greater than theirspacing in the rest or return state of the axle spring 51. Accordingly,the upper and lower axles 53, 55 push the indicator wheels 59, 61, 63and knock gears 103, 105, respectively, towards one another. A goodconnection between the indicator wheels 59, 61, 63 and knock gears 103,105 therefore results.

Also mountable in the cap part 31 of the outer casing 30 of the dosecounter module 19 is a drive wheel sub-assembly 150 of the countingmechanism. Referring to FIG. 2 to 6, the drive wheel sub-assembly 150comprises a drive wheel 151 having a pinion 153 having an outercircumference 155 defined by a series of teeth 157. The drive wheel 151further comprises a boss 159 extending axially from the left-hand sideof the pinion 153 (as viewed in e.g. FIG. 2). An axial passage orpassageway 161 extends through the pinion 153 and the boss 159.

The drive wheel 151 is a plastics component of the dose counter module19, e.g. of acetal, for instance made by injection moulding. The drivewheel sub-assembly 150 further comprises a drive wheel support spring163 made from a metal, such as stainless steel. The drive wheel supportspring 163 defines an axle section 165 which is insertable into theaxial passageway 161 of the drive wheel 151 for rotatable support of thedrive wheel 151.

The drive wheel sub-assembly 150 yet further comprises a slipping clutchspring 167, preferably formed from a metal, such as stainless springsteel. The clutch spring 167 is of a generally U-shaped configurationhaving a pair of generally parallel arm sections 169, 171 connected by aU-bend connector section 173. The connector section 173 biases the armsections 169, 171 to be closed together thereby enabling the armsections 169, 171 to be clamped onto the boss 159 of the drive wheel151, as shown in FIG. 9, for example. More particularly, one of the armsections 169 of the clutch spring 167 is formed with a curved portion175 adjacent its free end which is of complementary size and shape tothe outer circumferential surface 177 of the boss 159.

Thus, when the drive wheel 151 rotates on the axle section 165 of thedrive wheel support spring 163, the clutch spring rotates therewith.However, if a sufficient force is applied to the clutch spring 167 whichopposes its rotation with the drive wheel 151, the clutch spring 167slips on the boss 159. Therefore, the rotation of the drive wheel 151will not be transmitted to the slipping clutch spring 167.

FIG. 2 shows that the dose counting mechanism further comprises arotatable plastics pawl 200 (e.g. acetal) having a pawl arm 201 with apawl tooth 203 at its tip, a C-shaped hub 205 shaped to be rotatablymounted on the shaft 72 of the units wheel 59, and a boss 207 extendingaxially from the right-hand side of the rotatable pawl 200 which isadapted to be slidingly received in the track 174 defined between thearm sections 169, 171 of the clutch spring 167. The pawl may beinjection moulded.

The assembled state of the counting mechanism is shown in FIG. 7, andits arrangement in the cap part 31 of the outer casing 30 of the dosecounter module 19 is shown in FIGS. 4-6. The operation of the countingmechanism to show the number of metered doses of the medicinal aerosolformulation left will now be described.

When the aerosol canister unit 15 is in its rest position in theactuator 3, the counting mechanism of the dose counter module 19 is inthe state shown in FIGS. 8, 9 and 10A-B. More particularly, a rack 13projecting upwardly from a base surface of the actuator 3 extendsthrough an aperture 20 in the cap part 31 of the outer casing 30 of thedose counter module 19 so that a set of teeth 14 on the rack 13 meshwith the teeth 157 of the pinion 153 of the drive wheel 151. In thisregard, the drive wheel support spring 163 biases the drive wheel 151towards the window 25. The interaction of the rack 13 with the pinion153 causes the drive wheel 151 to be displaced against the biasing forceof the drive wheel support spring 163. This results in the pinion teeth157 being biased against the rack teeth 14 thereby ensuring a goodengagement therebetween.

In the rest position of the aerosol canister unit 15 in the actuator 3,the rotatable pawl 200 has an angular orientation relative to theratchet wheel 71 which results in the pawl tooth 203 engaging behind oneof the ratchet teeth 74.

If the aerosol canister unit 15 has been previously unused, theindicator wheels 59,61,63 are arranged on the upper axle 53 of the axlespring 51 so that the numerical indicia thereon are lined up to show inthe window 25 of the actuator 3 the starting number of metered dosesavailable in the aerosol canister 17 for dispensing. This startingnumber corresponds to the number of metered doses stated on the label ofthe aerosol canister 17, e.g. the “label claim”. As an example, thestarting number of metered doses may be ‘160’, as indicated in FIG. 15A.The label claim need not, however, match the actual number of availabledoses since an aerosol canister will usually be overfilled slightly toallow for losses during storage, for example. This also provides areserve of doses for a user once the counter has reached zero in case ofemergencies.

When a patient wishes to dispense a metered dose of the aerosolformulation, the patient places their lips on the mouthpiece 9 of theactuator 3 then simultaneously inhales and depresses the aerosolcanister unit 15 into the actuator 3. The start of this downstroke ofthe aerosol canister unit 15 into the actuator 3 is shown in FIGS.11A-B. In comparison FIGS. 10A-B shows the counting mechanism at rest.

The downstroke causes the dose counter module 19 to move downwardly inthe direction of arrow A relative to the rack 13 of the actuator 3. Thisrelative movement causes the teeth 14 of the rack 13 to rotate the drivewheel 151 in the direction of arrow B through its interaction with thepinion 153. The rotation of the drive wheel 151 causes the clutch spring167 mounted on the boss 159 to rotate therewith. This in turn causes therotatable pawl 200 to rotate on the shaft 72 of the units wheel 59 inthe direction of arrow C, which direction is opposite to the directionof rotation B of the drive wheel 151.

As will be appreciated from FIG. 11A, the rotation of the pawl 200 inthe direction of arrow C is caused through the location of the boss 207of the pawl 200 in the guide track 174 defined in the clutch spring 167.

As will be further appreciated from FIG. 11A, the rotation of the pawl200 in the direction of arrow C on the units wheel 59 causes the pawlarm 201 to disengage from behind the trailing surface of the ratchettooth 74 it was engaged with in the rest position, and to slide up theleading flank surface of the next adjacent ratchet tooth 74.

Continued depression of the aerosol canister unit 15 into the actuator 3causes the valve thereof to open, and for a metered dose of themedicinal aerosol formulation to be discharged from the mouthpiece 9,generally, in use, into the respiratory tract of the patient. As shownin FIG. 12A, the rotation of the pawl 200 on the units wheel 59 iscontinued until the pawl tooth 203 drops behind the trailing flanksurface of the next adjacent ratchet tooth 74. From this it will beappreciated that the pawl arm 201 is a resilient arm whereby the pawltooth 203 at the free end thereof falls from the tip of one ratchettooth 74 to the leading flank surface of the next adjacent ratchet toothduring the downstroke.

The rotation of the pawl 200 on the units drum 59 is not transmittedthereto due to a fixed pawl or resilient non-return leg 18 in the cappart 31 of the outer casing 30 of the dose counter module 19 engagingbehind the trailing flank surface of one of the ratchet teeth 74 of theratchet wheel 71 of the units wheel 59.

Comparison of FIG. 12A to FIG. 11A shows that the rotation of the pinion153 of the drive wheel 151 is able to be translated intocounter-rotation of the pawl 200 on the units wheel 59 through theability of the boss 207 of the pawl 200 to slide in the guide track 174defined in the clutch spring 167. In other words, there is a “togglelink”-type coupling between the drive wheel 151 and the pawl 200.

As further shown in FIG. 12A, when the rack 13 causes the pinion 153 torotate the drive wheel 151 a predetermined angle, the pawl 200 abutswith an end stop 221 which extends downwardly from the sleeve part 33 ofthe outer casing 30 of the dose counter module 19. This prevents thepawl 200 over-rotating on the units wheel 59 and the pawl tooth 203being indexed over more than one ratchet tooth 74 on the downstroke ofthe aerosol canister unit 15. Once the pawl 200 bears against the endstop 221, continued depression of the aerosol canister unit 15 into theactuator 3 (e.g. to open the valve) is accommodated by the clutch spring167 slipping on the boss 159 of the drive wheel 151 (as a result of theclutch spring 167 only being retained thereon by friction forces). Thatis to say, the drive wheel 151 is free to continue rotating once thepawl 200 abuts with the end stop 221 without this rotation beingtransmitted to the pawl 200 due to the drive wheel 151 rotating relativeto the clutch spring 167, i.e. there is a lost motion coupling.

Once the aerosol canister unit 15 has been depressed to the bottom ofits downstroke, and a metered dose of the medicinal aerosol formulationreleased, the patient releases, or reduces, the downward pressure on theaerosol canister unit 15 whereupon the biasing mechanism in the valveassembly of the aerosol canister 17 biases the aerosol canister unit 15back towards its rest position. The return stroke of the aerosolcanister unit 15 in the actuator 3 is shown schematically in FIGS.13A-B.

As shown, as the aerosol canister unit 15 is translated upwardly in thedirection of arrow D, the engagement of the rack 13 with the pinion 153causes the drive wheel 151 to rotate in an opposite direction (arrow E).The toggle-link coupling between the drive wheel 151 and pawl 200 causesthe pawl 200 to rotate in an opposite direction (arrow F). The rotationof the pawl 200 in the direction of arrow F causes the pawl arm 201 topull the units wheel 59 in the same direction through the engagement ofthe pawl tooth 203 with the trailing flank surface of the ratchet tooth74 which it dropped over on the downstroke of the aerosol canister unit15 in the actuator 3. In this regard, the fixed pawl 18 is resilientlyformed so that it is able to be flexed out of the way by one of theratchet teeth 74 and then drop behind that tooth 74 to preventcounter-rotation of the units wheel 59 at the end of the return strokeof the aerosol canister unit 15 in the actuator 3.

As shown in FIG. 9, once the rack 13 has caused the drive wheel 151 torotate a predetermined angular extent, the pawl 200 abuts with anotherend stop 66, this time presented by the cap part 31 of the outer casing30. This prevents the pawl 200 causing more than one ratchet tooth 74 topass the fixed pawl 18 on the return stroke of the aerosol canister unit15. If at this stage the return stroke of the aerosol canister unit isincomplete, i.e. the rest position has not been reached, the drive wheel151 is free to continue rotating relative to the slipping clutch spring167 in the direction of arrow E (through the engagement of the rack 13with the pinion 153).

The result of the rotation of the units wheel 59 in the direction ofarrow F is to cause the numerical indicia it displays in the window 25to be decreased by one, thereby indicating to the patient that there isnow one less metered dose left in the aerosol canister 17.

Thus, upon each actuation cycle of the aerosol canister unit 15, theunits wheel 59 is caused to be rotatably indexed by an angular amountsufficient to cause the previous units figure displayed in the window 25to be advanced and replaced by the next unit figure in the series, whichis one less than the previous figure. Bearing in mind that the numericalindicia on the units wheel 59 are equi-angularly spaced about thecircumference thereof, the units wheel 59 is rotatively indexed by 36°upon each actuation cycle of the aerosol canister unit 15. It will thusbe appreciated that the number of ratchet teeth 74 on the ratchet wheel71 corresponds to the number of numerical indicia on the units wheel 59,i.e. 10. It will further be appreciated that after each completerevolution of the units wheel 59 the same units figure is displayed inthe window 25.

As the units wheel 59 is rotatively indexed by the pawl-and-ratchetmechanism, the bunny tooth 77 of the units wheel 59 will engage theleft-hand side section 127 of the toothed wheel portion 11l of theright-hand knock gear 103 at the same point in each revolution of theunits wheel 59 on the upper axle 53. As indicated in FIG. 15A, the bunnytooth 77 is arranged on the units wheel 59 so that its engagement withthe left-hand side section 127 of the toothed wheel portion 111 of theright-hand knock gear 103 coincides with the number ‘0’ being displayedby the units wheel 59 in the window 25. The next actuation cycle of theaerosol canister unit 15 causes the bunny tooth 77 to transmit arotational force to the right-hand knock gear 103, through itsengagement with the left-hand side section 127 of its toothed wheelportion 111. The rotation imparted to the right-hand knock gear 103 bythe bunny tooth 77 of the units wheel 59 is transmitted to the tenswheel 61 through the meshing of the left-hand side section 127 of thetoothed wheel portion 111 with the teeth 87 of the tens wheel 61. Thenet result of this is that the numerical indicia displayed by the unitswheel 59 and tens wheel 61 are concurrently decremented by one. In thecase shown in FIGS. 15A-B, the result is to decrement the numberdisplayed in the window 25 from ‘160’ to ‘159’. This is also illustratedin FIGS. 14A-F.

During the transmission of the rotational indexing of the units wheel 59to the tens wheel 61 through the right-hand knock gear 103, theright-hand side section 123 of the toothed wheel portion ill of theright-hand knock gear 103 is received in a recess 78 (FIG. 15A) formedin the rim 65 of the units wheel 59 which is co-extensive with the gapbetween the ears of the bunny tooth 77.

As the tens wheel 61 is incrementally driven by the units wheel 59through the right-hand knock gear 103 at every complete rotation of theunits wheel 59 (when the ‘0’ decrements to ‘9’), the bunny tooth 93 onthe tens wheel 61 is advanced towards engagement with the left-handknock gear 105, specifically the left-hand side section 129 of thetoothed wheel portion 113 thereof. As before, when the tens wheel 61 isangularly positioned so that it displays the FIG. 10 in the window 25(at which point the units wheel 59 also displays its ‘0’ figure in thewindow 25), the bunny tooth 93 is disposed adjacent a tooth of theleft-hand side section 129 of the toothed wheel portion 113 of theleft-hand knock gear 105. The result of the next actuation cycle of theaerosol canister unit 15 is to cause the rotation or motion imparted tothe tens wheel 59, by the co-operation of the units wheel 59 and theright-hand knock gear 103, to be transmitted to the hundreds wheel 63 inlikewise manner. This results in the numerical indicia displayed by thehundreds wheel 63 in the window 25 being decrement by one, whereby thefull number displayed in the window by the drums sub-assembly 50 isdecremented by one from a number which is a factor of one hundred, e.g.‘100’ to ‘099’.

As will be understood from FIGS. 8 and 14A-F, when the tens wheel 61drives the hundreds wheel 63 through the left-hand knock gear 105, theright-hand side section 125 of the toothed wheel portion 113 of theleft-hand knock gear 105 is received in a recess 94 in the rim 67 of thetens wheel 61 which is co-extensive with the space between the ears ofthe bunny tooth 93.

In addition to the features of the counting mechanism described above,the counting mechanism further comprises a “lockout” arrangement whichlocks the drums sub-assembly 50 from being driven when each indicatorwheel 59, 61, 63 is angularly positioned on the upper axle 53 of theaxle spring 51 so that the display reads ‘000’. However, the lockoutarrangement is such as not to prevent the aerosol canister unit 15 stillbeing able to be actuated to dispense doses of medicinal aerosolformulation still remaining in the aerosol canister 17. In thisconnection, as a matter of routine, medicinal aerosol canisters areoverfilled (compared to the label claim) for safety issues. For example,for rescue medicaments, such as bronchodilators, it is imperative thatthe patient still be able to use the aerosol canister unit 15 after thelabel claim of metered doses has been used.

Referring now to FIGS. 4, 16A and 17A, for example, the hundreds wheel63 carries a peg 98 which, when the hundreds wheel 63 is angularlyoriented so as to display a ‘0’ in the window 25, abuts with a stop 42provided in the cap part 31 of the outer casing 30 of the dose countermodule 19. This abutment of the peg 98 with the stop 42 prevents furtherrotation of the hundreds wheel 63 by the pawl-and-ratchet drivemechanism. Moreover, the left-hand knock gear 105 is also locked fromfurther rotation due to its interengagement with the locked hundredswheel 63. So, once the hundreds wheel 63 has been locked by the abutmentof the peg 98 with the stop 42, the tens wheel 61 is able to completeone further revolution on the upper axle 53 before it too becomes lockedfrom further rotation through engagement of the bunny tooth 93 with theleft-hand knock gear 105. The locking of the tens wheel 61 furtherresults in the right-hand knock gear 103 being locked from furtherrotation due to its tooth engagement with the tens wheel 61. As will beunderstood, the tens wheel 61 becomes locked out when it too displays a‘0’ in the window 25.

Once the tens wheel 61 has been locked out, the units wheel 59 is ableto complete just one more revolution for it to display a ‘0’ in thewindow 25. The units wheel 59 then in turn becomes locked out by theinterengagement of its bunny tooth 77 with the right-hand knock gear103. See FIGS. 16A-F.

If a patient wishes to use the aerosol canister unit 17 after the drumssub-assembly 50 has been locked out, the actuation cycle is still ableto be completed through the clutch spring 167 slipping on the boss 159of the drive wheel 151. In other words, the drive system is disconnectedfrom the drum sub-assembly 50 by the slipping clutch 167. This is shownschematically in FIG. 17B.

Referring now to FIGS. 18 to 21, a preferred sleeve part 33 is shown.This sleeve part 33, like the one shown in FIGS. 1 to 3, is adapted tobe attached to a cap part 31 (see FIG. 5) to form a casing for a dosecounter module 19. It has four holes 131, 132, 133, 134 for receivingposts 35 on the cap part 31. Two of the holes 131, 132 are cylindricalfor receiving cylindrical posts 35. The other two holes are generallycylindrical but with a flattened part (i.e. generally D shaped) forreceiving correspondingly shaped posts 35 on the cap part 31.

The two non-cylindrical holes 133, 134 are relatively rotated so thatthe cap part 31 can only be fitted in one orientation even if the posts35 are symmetrically arranged.

Differently shaped holes could be provided, and would need to beprovided for differently shaped posts 35 such as those shown in FIG. 4(only one post 35 is non-cylindrical) or FIG. 3 (the posts 35 have asquare section, with hook clips 37 on the ends thereof).

Two posts 135 are also provided on the sleeve part 33 extending from thebottom 137 thereof. These posts 135 engage into holes 136 provided inthe cap part 31 (see FIG. 5). The posts 135 on the sleeve part 33 areshorter than the posts 35 on the cap part 31.

The sleeve part 33 is generally cylindrical. However, in the bottom 137,there is moulded a base moulding having a generally U-shapedconfiguration to match the U-shaped configuration of the cap part 31defined by the concave cut-out 41 (see, e.g., FIG. 4). This U-shapedbase moulding further defines the position for the canister's valve stem27 (see FIGS. 22 and 23) and the stand or stem block 13 (described abovewith reference to the prior art) to fit into. Further it defines part ofthe protrusion 23 described above (the protrusion 23 receives the window25).

The base moulding extends from the bottom 137 of the sleeve part 33 upto a base wall 139. The outlet end of the canister 17 may, in use, restagainst an upper side of this base wall 139 (or on supports providedthereon), as will be described with reference to FIGS. 22 and 23 below.The moulding, on its lower side, however, provides, in combination withthe cap part 31, a cavity into which the indexing or counting mechanism,such as the drums sub-assembly 50, can be fitted. See FIGS. 22 and 23.

The cylindrical portion 140 of the sleeve part 33 can accept more thanone style of canister 17, in this embodiment different styles of valveassembly. As an example, FIG. 22 shows a canister 17 which is fittedwith a first type of valve assembly 250. FIG. 23 shows the canister 17fitted with a second, different type of valve assembly 300 (i.e. the canis the same, but the valve assembly differs). As will be seen, thevalves 250,300 have valve stem ends 29 (or ferrules) of different shape.In the first valve assembly 250, there is a small nose 49 adjacent thevalve stem 27. The nose 49 of the second valve assembly 300, however, ismuch longer, axially. Moreover, the valve assemblies 250, 300 protrudefrom the associated cans by a different distance D1, D2, i.e. the valveassemblies 250, 300 have a different thickness. So, the valve stems 27are spaced outboard from the can at different distances D1, D2.

As a result of these differences, the canisters 17 sit differently inthe sleeve part 33. However, it is important that the tip of each valvestem 27 be positioned at a common, or substantially common, positionrelative to a reference surface of the dose counter module 19, e.g. thebase wall 139. In other words, the spatial position of the tip of eachvalve stem 27 in the dose counter module 19, when assembled to therespective aerosol canister 17, must be the same, or substantially thesame. Expressed another way, the valve stems 27 must be spaced at thesame, or substantially same, distance from the reference surface of thedose counter module 19.

To this end, the upper side of the base wall 139 has two differentlysized concentric supports or ledges 141, 142. The first ledge 141comprises an annulus (see FIG. 20) extending upwards from the base wall139. It has an appropriate height to support, in use, the first valveassembly 250, as shown by arrow 143 in FIG. 22. The second ledge 142comprises a smaller annulus extending upwards from the base wall 139. Itis concentric with the first ledge 141. However, it extends upwards to alesser extent. It is adapted to support, in use, the second valveassembly 300, as marked by arrow 144 in FIG. 23.

The base wall 139 also comprises an aperture 145 in its centre,concentric with the two annuluses. The aperture 145 allows the valvestem 27 of the canister 17 to extend through the base wall 139 so thatit can be inserted into the stand or stem block 333.

As shown in FIGS. 22 and 23, the ledges 141, 142 respectively supportthe first and second valve assemblies 250, 300 in the sleeve part 33such that the valve stems 27 extend through the aperture 45 by the samedistance, or substantially the same distance.

In this way, the rest positions in the actuator 3 of the aerosolcanister units 15 incorporating the different valve assemblies 250,300is the same, or substantially the same. This is because the spatialposition of the valve stem tips in the respective dose counter module 19is the same.

The sleeve part 33 also comprises a split ring collar 43, as previouslydescribed, for assisting in the connection of the sleeve part 33 to thecanister 17 via the neck 47, which is annular. The wall 147 of thecylindrical portion 140 of the sleeve part 33 has an internal wallsurface having a step or shoulder 146 for resting the collar 43 on. FIG.3 shows this as a separately made ledge that is attached to the internalwall surface. The shoulder 146 assists in locating the collar 43correctly for adhering or welding it to the sleeve part 33 for securingthe canister 17 in the sleeve part 33 with the correct depth ofinsertion.

The top 138 of the wall 147 is chamfered also to assist in the insertionof the collar 43 and canister 17 into the sleeve part 33.

The above described components all can easily be fabricated and can beassembled using automated apparatus. Therefore they provide a more costeffective solution than the prior art.

Although the pMDI 1 described above with reference to the FIGURES ofdrawings is shown for oral inhalation, the mouthpiece 9 may be replacedwith a nozzle for insertion into a patient's nostril, i.e. forintra-nasal use. The therapeutic agent contained in the aerosol canister17 may for the treatment of mild, moderate or severe acute or chronicsymptoms or for prophylactic treatment. The therapeutic agent ispreferably for treating respiratory diseases, e.g. asthma, chronicobstructive pulmonary disease (COPD), although may be for othertherapeutic indications, e.g. treating rhinitis.

Appropriate therapeutic agents or medicaments may thus be selected from,for example, analgesics, e.g., codeine, dihydromorphine, ergotamine,fentanyl or morphine; anginal preparations, e.g., diltiazem;antiallergics, e.g., cromoglycate (e.g. as the sodium salt), ketotifenor nedocromil (e.g. as the sodium salt); antiinfectives e.g.,cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclinesand pentamidine; antihistamines, e.g., methapyrilene; anti-inflammatories, e.g., beclomethasone (e.g. as the dipropionate ester),fluticasone (e.g. as the propionate ester), flunisolide, budesonide,rofleponide, mometasone (e.g. as the furoate ester), ciclesonide,triamcinolone (e.g. as the acetonide), 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioicacid S-(2-oxo-tetrahydro-furan-3-yl) ester or 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester; antitussives, e.g., noscapine;bronchodilators, e.g., albuterol (e.g. as free base or sulphate),salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g.as hydrobromide), formoterol (e.g. as fumarate), isoprenaline,metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. asacetate), reproterol (e.g. as hydrochloride), rimiterol, terbutaline(e.g. as sulphate), isoetharine, tulobuterol or4-hydroxy-7-[2-([2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)benzo-thiazolone; PDE4 inhibitors e.g. cilomilast or roflumilast;leukotriene antagonists e.g. montelukast, pranlukast and zafirlukast;[adenosine 2a agonists, e.g. 2R, 3R, 4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol(e.g. as maleate)]; [α4 integrin inhibitors e.g.(2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbony}oxy)phenyl]-2-[((2S)-4-methyl-2-{[2-(2-ethylphenoxy)acetyl]amino)pentanoyl)amino]propanoicacid (e.g as free acid or potassium salt)), diuretics, e.g., amiloride;anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium,atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone orprednisolone; xanthines, e.g., aminophylline, choline theophyllinate,lysine theophyllinate or theophylline; therapeutic proteins andpeptides, e.g., insulin or glucagons. It will be clear to a personskilled in the art that, where appropriate, the medicaments may be usedin the form of salts, (e.g., as alkali metal or amine salts or as acidaddition salts) or as esters (e.g., lower alkyl esters) or as solvates(e.g., hydrates) to optimise the activity and/or stability of themedicament and/or to minimise the solubility of the medicament in thepropellant.

Preferably, the medicament is an anti-inflammatory compound for thetreatment of inflammatory disorders or diseases such as asthma andrhinitis.

Preferably, the medicament is formulated in a hydrofluoroalkanepropellant, such as HFA-134a or HFA-227 or a combination thereof.

Preferably, the medicament is an anti-inflammatory steroid, such as acorticosteroid, for instance fluticasone, e.g. as the propionate ester,or a long acting beta agonist (LABA), such as salmeterol, e.g. as thexinafoate salt, or a combination thereof.

Preferred medicaments are salmeterol, salbutamol, albuterol, fluticasoneand beclomethasone and salts, esters or solvates thereof, for instancefluticasone propionate, albuterol sulphate, salmeterol xinafoate andbeclomethasone diproprionate.

The medicament may also be a glucocorticoid compound, which hasanti-inflammatory properties. One suitable glucocorticoid compound hasthe chemical name: 6α,9α-Difluoro-17α-(1-oxopropoxy)-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester (fluticasone propionate). Another suitableglucocorticoid compound has the chemical name: 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester. A further suitable glucocorticoid compoundhas the chemical name: 6α,9α-Difluoro-11β-hydroxy-16α-methyl-17β-[(4-methyl-1,3-thiazole-5-carbonyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioicacid S-fluoromethyl ester.

Other suitable anti-inflammatory compounds include NSAIDs e.g. PDE4inhibitors, leukotriene antagonists, iNOS inhibitors, tryptase andelastase inhibitors, beta-2 integrin antagonists and adenosine 2aagonists.

The medicaments may be delivered in combinations. As an example, theremay be provided salbutamol (e.g. as the free base of the sulphate salt)or salmeterol (e.g. as the xinafoate salt) in combination with ananti-inflammatory steroid, such as beclomethasone (e.g. as an ester,preferably dipropionate) or fluticasone (e.g. as an ester, preferablypropionate).

The actuation indicator of the present invention is not limited for usewith an aerosol container, as in the example described with reference tothe FIGURES of drawings, but may be used with other types of dispensingdevice. Moreover, the dispensing device need not necessarily be fordispensing medicament.

The present invention has been described above purely by way of example.Modifications, in detail, however, may be made within the scope of theinvention, as defined in the claims appended hereto.

For the avoidance of doubt, the use of words herein such as“substantially”, “generally”, “about” and the like in relation toparameters or properties etc. is meant to encompass the absoluteparameter or property as well as non-consequential deviations therefrom.

1. An axle of a rotatable element of an actuation indicator, wherein theaxle is provided by a spring that is adapted in use to bias therotatable element towards another element of the actuation indicatorwith which the rotatable element is engaged.
 2. The axle of claim 1,wherein the rotatable element is a pinion.
 3. The axle of claim 2,wherein the other element with which the pinion engages is a rack. 4.The axle of claim 1, wherein the rotatable element is an indicator wheelfor indicating actuation of a device with which the indicator isassociated.
 5. The axle of claim 4, wherein there are at least tworotatable elements on the same axle.
 6. The axle of claim 4, wherein theother element is a rotatable element mounted on a second axle, thesecond axle optionally being provided by the spring.
 7. An assemblycomprising the axle of claim 1, the or each rotatable element on theaxle and the other element.
 8. The axle of claim 6, wherein the springcomprises the second axle and a biasing section connecting the two axlesto bias them together.
 9. An actuation indicator comprising a drumssub-assembly comprising a rotatable actuation indicator wheel, arocking, ratchet pawl for rotating the indicator wheel in a setdirection and a rocking mechanism for the pawl driven by a slippingclutch arrangement, wherein the slipping clutch arrangement comprises aslipping clutch spring engaged at one end to a pinion of a rack andpinion assembly and at a second end to the ratchet pawl.
 10. Theactuation indicator of claim 9, wherein the slipping clutch spring has agenerally U-shaped configuration.
 11. The actuation indicator of claim10, wherein the open end of the spring engages a boss of the pinion andthe closed end of the spring defines a track for slidingly engaging aboss provided on the pawl.
 12. The actuation indicator of claim 9,wherein the ratchet pawl engages a ratchet wheel that is fixed to theindicator wheel.
 13. The actuation indicator of claim 12, wherein aresilient, non-return leg engages a tooth of the ratchet wheel toprevent rotation of the ratchet wheel in a direction other than the setdirection, and the non-return leg rides up and over the teeth to allowrotation in the set direction.
 14. The actuation indicator of claim 9wherein there are at least two indicator wheels arranged to sequentiallycount down from a set figure to zero, wherein the indicator wheels lockfrom further rotation in the set direction when they have counted downto zero, the slipping clutch spring then slipping on further attempts torotate the mechanism.
 15. A casing adapted to be attached over a valvestem end of a canister to form a canister unit, the casing comprising asleeve part having a generally cylindrically shaped section having agenerally cylindrical inner surface extending from a top of the sleevepart towards a base wall, and a collar affixable around a neck of thecanister, and sized, when around the neck of the canister, to fitthrough the top of the sleeve part, into the sleeve part, whereat itwill contact at least a portion of the generally cylindrical innersurface, wherein the generally cylindrical inner surface has a shoulderfor supporting the collar to prevent the collar from being insertedfurther into the sleeve part, the shoulder being spaced from the top andthe base wall of the sleeve part.
 16. The casing of claim 15, whereinthe top of the sleeve part comprises a chamfered surface to assist withthe insertion of the collar into the sleeve part.
 17. The casing ofclaim 15, wherein the shoulder is formed by an annular step in thegenerally cylindrical inner surface.
 18. The casing of claim 15, whereinthe shoulder is formed by a ledge attached to the generally cylindricalinner surface.
 19. The casing of claim 15, wherein the collar is a splitring collar.
 20. The casing of claim 15, wherein the collar, in anassembled canister unit, is welded to the sleeve part.
 21. A casingadapted to be attached over a valve stem end of a canister to form acanister unit, the casing comprising a sleeve part for receiving acanister and a cap part for receiving a counter assembly of a dosecounter for the canister unit, wherein the cap part and counter assemblycan be assembled together separate from the sleeve part and canister,the sleeve part and cap part then being joinable together to form thecasing.
 22. The casing of claim 21, further comprising a counterassembly, the counter assembly comprising a drums sub-assembly. 23.(canceled)
 24. The casing of claim 21, wherein the sleeve part isadapted to receive more than one form of valve stem end.
 25. The casingof claim 24, wherein the sleeve part comprises a top through which, inuse, a valve stem end of the canister will be inserted and a base wallspaced from the top having more than one support thereon, each supportadapted to support a different form of valve stem end, whereby more thanone valve stem end is supportable in the sleeve part.
 26. The casing ofclaim 25, wherein the supports are annular ledges.
 27. The casing ofclaim 26, wherein the ledges are concentric.
 28. The casing of claim 25,wherein a first support is of a first height above the base wall and thesecond support is of a lesser height above the base wall.
 29. (canceled)30. A sleeve part for receiving a valve stem end of a canister, thesleeve part being adapted to receive more than one form of valve stemend.
 31. The sleeve part of claim 30, wherein the sleeve part comprisesa top through which, in use, a valve stem end of the canister will beinserted and a base wall spaced from the top having more than onesupport thereon, each support being for supporting a different form ofvalve stem end, whereby more than one form of valve stem end is able tobe supported in the sleeve part.
 32. The sleeve part of claim 31,wherein the supports are annular ledges.
 33. The sleeve part of claim32, wherein the ledges are concentric.
 34. The sleeve part of claim 31,wherein a first said support is of a first height above the base walland a second said support is of a lesser height above the base wall. 35.A drug product for dispensing a drug formulation comprising a propellantand a medicament comprising: a housing; a container containing the drugformulation having an outlet member and adapted to be actuable withinthe housing; and, an actuation indicating assembly, fixedly attached tothe container, comprising: a body cradle having a post; a drive wheeladapted to engage the post and to frictionally engage a slipping clutch;a ratchet pawl adapted to engage the slipping clutch; a star wheeladapted to engage the ratchet pawl; and one or more drums adapted toengage the star wheel; wherein the fixedly attached container andactuation indicating assembly are reversibly removable from the housingas a single unit.
 36. The drug product of claim 35, comprising threedrums adapted to display a count of 000 to 999, and further comprisingan arm affixed to a hundred's drum adapted to contact a stop, whereinthe slipping clutch is adapted to frictionally slip when the countreaches
 000. 37. The drug product of claim 35, comprising a hundred'sdrum having numerals 0, 1 and 2, a ten's drum having numerals 0 through9 and a one's drum having numerals 0 through
 9. 38. The drug productaccording to claim 35, wherein the actuation indicating assemblyincludes one or more grip members adapted to fixedly engage a neckportion of the container.
 39. The drug product according to claim 35,wherein the housing includes a mouthpiece.
 40. The drug productaccording to claim 39, wherein the housing includes a passage adapted topass doses from the container to the mouthpiece.
 41. The drug productaccording to claim 35, wherein the container includes a metering valveadapted to dispense metered doses.
 42. The drug product according toclaim 35, further including a window adapted to display numerals on oneor more drums engaging the star wheel.
 43. The drug product according toclaim 35, wherein the actuation indicating assembly is fixed to thecontainer by an adhesive, a welded shrink sleeve, a heat form, a crimp,an ultrasonic weld, an o-ring elastomer, or a split-ring collar.
 44. Thedrug product of claim 35, wherein the actuation indicating assembly ispermanently fixed to the container.
 45. The drug product of claim 35,wherein the medicament is selected from the group consisting ofbeclomethasone, fluticasone, flunisolide, budesonide, rofleponide,mometasone, triamcinolone, noscapine, albuterol, salmeterol, ephedrine,adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol,terbutaline, tiotropium, ipratropium, phenylephrine,phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine,tulobuterol,(-)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl}methyl}benzenemethanol, esters, solvates and salts thereof, andcombinations thereof.
 46. The drug product of claim 45, wherein themedicament is albuterol sulphate.
 47. The drug product of claim 45,wherein the medicament is salmeterol xinafoate.
 48. The drug product ofclaim 45, wherein the medicament is fluticasone propionate.
 49. The drugproduct of claim 45, wherein the medicament is beclomethasonedipropionate.
 50. The drug product of claim 45, wherein the medicamentis the combination of salmeterol xinafoate and fluticasone propionate.51. The drug product of claim 45, wherein the medicament is salmeterolxinafoate and a salt, ester or solvate of ipratropium.
 52. The drugproduct of claim 35, wherein the housing is constructed frompolypropylene.
 53. The drug product of claim 35, wherein one or morecomponents of the actuation indicating assembly are constructed frompolypropylene.
 54. The drug product of claim 35, further comprising oneor more knock gears adapted to engage the one or more drums.
 55. Thedrug product of claim 54, comprising first, second and third drums andfirst and second knock gears.
 56. A method of patient compliancecomprising the acts of: providing the drug product of claim 35,administering the drug formulation to a patient, counting down a numberof available doses remaining in the container on the actuationindicating assembly, and indicating the number of available dosesremaining in the container to the patient.
 57. The method of claim 56,wherein the container is over-filled with up to 40 actuations.
 58. Themethod of claim 56, wherein the actuation indicating assembly locks outwhen the count reaches 000 and the drug product remains actuable for upto 40 subsequent actuations.
 59. A drug product for dispensing a drugformulation comprising a propellant and a medicament comprising: ahousing; a container containing the drug formulation having an outletmember and adapted to be actuable within the housing; and an actuationindicating assembly, fixedly attached to the container, comprising: abody cradle having a post; a means for driving a slipping clutch meansadapted to engage the post and to frictionally engage the slippingclutch means for grasping a ratcheting means; a pawl means forratcheting a star wheel adapted to engage the slipping clutch means; astar wheel adapted to engage the pawl ratcheting means; and one or moredrums adapted to engage the star wheel; wherein the fixedly attachedcontainer and actuation indicating assembly are reversibly removablefrom the housing as a single unit.
 60. The drug product of claim 59,comprising first, second and third drums, and further comprising a meansfor stopping the first drum.
 61. The drug product of claim 59, furthercomprising a first means for knock locking the first and second drums,and a second means for knock locking the second and third drums.
 62. Thedrug product of claim 59, further adapted to indicate a count of 000 to999, and further adapted to lock the drums when the count indicates 000.63-69. (canceled)